Stated goals of the NINDS are to "unravel the complexities of information transfer within the brain" and encourage "further study of ion channel structure and function." In neurons of the CNS, it is still not well understood how ion channels of the soma convert time-varying membrane currents from the dendritic arbor into action potential spike trains that are transmitted along axons. The overall goal of this research project is to understand how statistics of membrane potentials are encoded in spike trains and specifically how somatic ion channels of a neocortical pyramidal neuron can encode information about the mean and variance of the membrane potential in the spiking output of action potentials. Specifically, the aims are to (1) find ion channel characteristics that lead to spiking primarily in response to the input mean in contrast to spiking that results primarily due to input fluctuations, (2) determine how the adaptation of the mean firing rate changes according to changes in the time-varying stimulus means and variances, and (3) investigate the utility of keeping track of interspike intervals to code for time-varying input means and variances instead of using only the mean firing rate. These aims will be accomplished by developing and applying novel theoretical approaches to data obtained from single neuron recordings of neocortical rat pyramidal neurons. The ability to functionally assess the health of a neuron would greatly assist in clinical treatment of neurological disorders from Alzheimer's disease to epilepsy, but there is currently no way to measure a neuron's functional health. In part, this is because the neural code, which defines how neurons transmit information, is not understood;unlike the DMA code, where much is known about how nucleic acids determine protein structure, little is known about what action potentials in CNS neurons really mean. This project seeks to define an aspect of the neural code that is immediately involved in the production of neuronal spikes, which are the "letters" of the neural code. The goal is to directly relate biophysical properties such as ion channel densities to the information processing that the neuron does. Eventually, since at least some biophysical properties may be determined from genetic analyses, it may be possible to use such analyses to evaluate the function of diseased neurons.